Evidence map›Paper›PMID 38898050›Full record

ArticleNature communications2024

The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer.

Pengfei Yan, Xi Lin, Lijie Wu, Lu Xu, Fei Li, Junlin Liu, Fei Xu

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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  3. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Pengfei Yan *iHuman Institute, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0009-0009-9005-7628
Xi Lin *iHuman Institute, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0002-9712-1882
Lijie WuiHuman Institute, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0002-2253-0497
Lu XuiHuman Institute, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0009-0007-4481-3125
Fei LiiHuman Institute, ShanghaiTech University, Shanghai, China.ORCID http://orcid.org/0000-0002-4991-0043
Junlin LiuiHuman Institute, ShanghaiTech University, Shanghai, China.
Fei XuiHuman Institute, ShanghaiTech University, Shanghai, China. xufei@shanghaitech.edu.cn.ORCID http://orcid.org/0000-0003-0719-3901

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32071194
6 · The paper itself

Abstract

GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor's structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Indexed as

Multiple MyelomaProtein MultimerizationReceptors, G-Protein-CoupledSingle-Chain AntibodiesAntibodies, MonoclonalBinding SitesHumansProtein BindingAntibodies, MonoclonalReceptors, G-Protein-CoupledSingle-Chain Antibodies

Identifiers

PMID38898050
PMCPMC11187071

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.